Messenger ribonucleic acid, or mRNA, is a single-stranded molecule that plays a temporary but central role in the mechanics of a cell. Its function is to act as an intermediary, carrying the genetic instructions from the cell’s DNA to the protein-making machinery. This molecular blueprint is copied from a specific gene and then used as a template to construct a protein. Understanding the historical context of this molecule’s discovery illuminates how scientists pieced together the process of life itself. The search for this specific genetic carrier was a defining moment in the field of molecular biology.
The Molecular Mystery
The mid-twentieth century brought a clear understanding of the major cellular components involved in heredity and function. Scientists knew that the genetic code was stored in DNA, which in complex cells is safely contained within the nucleus. The actual manufacturing of proteins, however, was known to occur outside the nucleus in the cytoplasm, specifically on small structures called ribosomes. This spatial separation presented a significant puzzle: how could the instructions stored in the DNA in one location be safely and effectively delivered to the protein-building ribosomes in another area of the cell?
The existing models did not account for this necessary transit of information. One theory suggested that the DNA itself might temporarily travel out of the nucleus, while another proposed that the ribosomes were specialized for each gene. Neither of these hypotheses aligned with observed cellular efficiency and the rapid changes in protein production seen in certain biological processes. The scientific community began to hypothesize that an intermediary molecule must exist—a transient copy of the DNA’s code that could move to the cytoplasm without risking the permanent genetic archive. This theoretical molecule needed to be unstable and short-lived, ensuring that protein production could be quickly switched off when necessary.
The Pivotal 1961 Breakthrough
The initial evidence for this transient molecule emerged earlier than the definitive confirmation. In 1956, researchers Elliot Volkin and Lazarus Astrachan observed a rapidly produced, unstable form of RNA in E. coli bacteria after they were infected by a bacteriophage virus. This newly synthesized RNA had a base composition that closely matched the viral DNA, suggesting it was a copy of the invading genetic material. They termed this finding “DNA-like RNA,” but its exact function as a message carrier remained unclear at the time.
The concept was solidified in 1960 when Sydney Brenner, François Jacob, and Francis Crick proposed that the information-carrying molecule must be an unstable form of RNA that associated with the existing ribosomes. This idea led to a highly focused experiment designed to test the messenger hypothesis directly. The definitive experimental proof was published in the journal Nature in May 1961, in a paper by Brenner, Jacob, and Matthew Meselson.
The team used a sophisticated technique involving heavy and light isotopes and bacteriophage infection to track the movement of genetic material. They infected bacteria that had been grown in a “heavy” medium, making their ribosomes dense, and then transferred them to a “light” medium for the infection. The results clearly showed that any newly synthesized, unstable RNA was associated with the existing “heavy” ribosomes. This proved that the ribosomes were general-purpose protein factories, and the new, unstable RNA was the template carrying the viral instructions. Concurrent findings published in the same issue of Nature by François Gros and his colleagues further supported the existence of this messenger molecule.
Formalizing the Concept
The confirmation of this intermediate molecule immediately required a formal name and classification to distinguish it from the other known forms of RNA. François Jacob and Jacques Monod coined the term “messenger RNA,” or mRNA, as early as 1960 during the conceptual stage of their work. This name accurately reflected its function as the carrier of the genetic message from the gene to the site of protein synthesis.
Prior to this, two other major classes of RNA were already recognized: ribosomal RNA (rRNA), which forms the structural and enzymatic core of the ribosome, and transfer RNA (tRNA), which brings the correct amino acids to the ribosome. The identification and naming of mRNA completed the picture, categorizing the three necessary forms of RNA required for protein production. This three-part distinction allowed scientists to clearly model the flow of genetic information: DNA is transcribed into mRNA, and the mRNA is then translated into protein with the help of rRNA and tRNA.
Foundational Shift in Biology
The discovery of messenger RNA changed how scientists viewed gene expression and cellular control. Before 1961, the mechanism for turning genes on and off was poorly understood, with some theories suggesting the entire ribosome structure was regulated. Confirming the existence of a short-lived, rapidly degraded mRNA provided a simple and elegant explanation for gene regulation.
Cells could now be understood to control protein synthesis by regulating the production of the unstable mRNA copy. If a cell needed to stop making a protein, it simply had to stop transcribing the gene into mRNA, and the existing messenger molecules would quickly break down. This realization provided the molecular basis for understanding how cells can adapt their protein profile rapidly in response to environmental changes or developmental signals. The mRNA concept paved the way for subsequent research into the regulation of gene transcription.